Vascular Effects of Triglyceride-rich Lipoproteins

This study has been completed.
Sponsor:
Collaborator:
Royal Veterinary College
Information provided by (Responsible Party):
Dr Wendy Hall, King's College London
ClinicalTrials.gov Identifier:
NCT01618071
First received: June 8, 2012
Last updated: October 10, 2012
Last verified: October 2012
  Purpose

Many types of cardiovascular disease begin when the layer of cells lining blood vessels (endothelial cells) start to function abnormally. This causes white blood cells (monocytes) to enter the blood vessel wall and eventually form lesions. Fats from foods we consume are carried in the blood for 3-8 hours after a fatty meal in small particles known as chylomicrons (CM) and chylomicron remnants (CMR). The overall aim of this project is to investigate the idea that n-3 polyunsaturated fatty acids (PUFA) protect against heart disease by modifying the effect of CMR on endothelial cells and monocytes. We hypothesize that n3-PUFA carried in CMR reduce detrimental events which promote blood vessel damage and activate protective mechanisms to improve the function of arteries.


Condition Intervention
Postprandial Period
Lipemia
Vasodilation
Vascular Resistance
Nitric Oxide
Dietary Supplement: High-fat meals varying in their fatty acid composition

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Unravelling the Mechanisms of Vascular Protection by n3-PUFAs to Optimise and Support Their Use as Bioactives by the Food Industry

Resource links provided by NLM:


Further study details as provided by King's College London:

Primary Outcome Measures:
  • Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction [ Time Frame: 6 h post-meal ] [ Designated as safety issue: No ]
    The primary outcome of the study is activation of inflammatory/oxidative stress pathways within cultured endothelial cells following incubation with pooled postprandial lipoprotein fractions rich in chylomicron remnants. Due to the nature of this type of research this necessitates more than one primary outcome measure: the primary measures are NF-kappa-beta activation, cytokine production (e.g. interleukin-6) and reactive oxygen species generation in the cultured human endothelial cells.


Secondary Outcome Measures:
  • Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol [ Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal ] [ Designated as safety issue: No ]
  • Incremental area under the plasma concentration versus time curve (iAUC) of glucose [ Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal ] [ Designated as safety issue: No ]
  • Incremental area under the plasma concentration versus time curve (iAUC) for non-esterified fatty acids [ Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal ] [ Designated as safety issue: No ]
  • Incremental area under the plasma concentration versus time curve (iAUC) for plasma fatty acid composition (%) [ Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal ] [ Designated as safety issue: No ]
  • Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol [ Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal ] [ Designated as safety issue: No ]
  • Incremental area under the unit measure versus time curve for brachial augmentation index [ Time Frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal ] [ Designated as safety issue: No ]
  • Incremental area under the unit measure versus time curve for systolic blood pressure [ Time Frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal ] [ Designated as safety issue: No ]
  • Incremental area under the unit measure versus time curve for diastolic blood pressure [ Time Frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal ] [ Designated as safety issue: No ]
  • Change in digital volume pulse stiffness index [ Time Frame: 0, 2, 4 and 6 h post-meal ] [ Designated as safety issue: No ]
  • Change in digital volume pulse reflection index [ Time Frame: 0, 2, 4 and 6 h post-meal ] [ Designated as safety issue: No ]
  • Change in plasma nitrite/nitrate concentrations [ Time Frame: 0, 2, 4 and 6 h ] [ Designated as safety issue: No ]
  • Change in plasma 8-isoprostane F2alpha concentrations [ Time Frame: 0, 2, 4 and 6 h post-meal ] [ Designated as safety issue: No ]
  • Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 4 h postprandial chylomicron remnant-rich lipoprotein fraction [ Time Frame: 4 h post-meal ] [ Designated as safety issue: No ]
  • Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 5 h postprandial chylomicron remnant-rich lipoprotein fraction [ Time Frame: 5 h post-meal ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: June 2012
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Oleic acid
75 g high oleic acid sunflower oil.
Dietary Supplement: High-fat meals varying in their fatty acid composition
70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Other Names:
  • DHASCO
  • Purified fish oil
Active Comparator: Linoleic acid
75 g high linoleic acid sunflower oil.
Dietary Supplement: High-fat meals varying in their fatty acid composition
70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Other Names:
  • DHASCO
  • Purified fish oil
Experimental: Eicosapentaenoic acid and docosahexaenoic acid
5 g EPA and DHA derived from fish oil, made up to a total of 75 g with high oleic sunflower oil.
Dietary Supplement: High-fat meals varying in their fatty acid composition
70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Other Names:
  • DHASCO
  • Purified fish oil
Experimental: Docosahexaenoic acid
5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.
Dietary Supplement: High-fat meals varying in their fatty acid composition
70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Other Names:
  • DHASCO
  • Purified fish oil

  Eligibility

Ages Eligible for Study:   35 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy males
  • Non-smokers
  • Aged 35-70 years
  • Fasting TAG concentrations ≥1.2 mmol/L.

Exclusion Criteria:

  • Reported history of CVD (myocardial infarction, angina, venous thrombosis, stroke), impaired fasting glucose/uncontrolled type 2 diabetes (or fasting glucose ≥ 6.1 mmol/L), cancer, kidney, liver or bowel disease.
  • Presence of gastrointestinal disorder or use of drug, which is likely to alter gastrointestinal motility or nutrient absorption.
  • History of substance abuse or alcoholism (previous weekly alcohol intake >60 units/men)
  • Current self-reported weekly alcohol intake exceeding 28 units
  • Allergy or intolerance to any component of test meals
  • Unwilling to restrict consumption of any source of fish oil for the length of the study
  • Weight change of >3kg in preceding 2 months
  • Body Mass Index <20 and >35 kg/m2
  • Fasting blood cholesterol > 7.8 mmol/L
  • Current cigarette smoker.
  • Current use of lipid lowering medication
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01618071

Locations
United Kingdom
Diabetes & Nutritional Sciences Division, King's College London
London, United Kingdom, SE1 9NH
Sponsors and Collaborators
King's College London
Royal Veterinary College
Investigators
Principal Investigator: Wendy L Hall, PhD King's College London
  More Information

Publications:

Responsible Party: Dr Wendy Hall, Lecturer in Nutritional Sciences, King's College London
ClinicalTrials.gov Identifier: NCT01618071     History of Changes
Other Study ID Numbers: DRINC 11-LO-0116, BB/1005862/1
Study First Received: June 8, 2012
Last Updated: October 10, 2012
Health Authority: UK: National Research Ethics Service

Keywords provided by King's College London:
n-3 PUFA
Endothelial cells
Nitric oxide
Oxidative stress
Blood pressure
Vasodilation
Lipemia
Unsaturated dietary fats

ClinicalTrials.gov processed this record on October 01, 2014